Clinical Trial: Safety and Dose Ranging Study of Human Insulin Receptor MAb-IDUA Fusion Protein in Adults and Children With MPS I

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Two-Stage, Phase 1/2, Open-Label Study of the Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Patients With Mucopo

Brief Summary:

AGT-181 is a fusion protein containing alpha-L-iduronidase that is intended to deliver the enzyme peripherally and to the brain, when administered intravenously. This is a safety and tolerability study to obtain safety and exposure data as well as information on the biological activity of the investigational drug.

This is a two-stage, sequential, single and multi-dose study of AGT-181 in patients with MPS I. The first stage will be an open-label, single-dose, dose-escalation cohort study and the second stage will be an open-label, multi dose, adaptive dose escalation cohort study.


Detailed Summary:

Stage 1:

Stage one will be a single-dose, dose-escalation study in cohorts of 2 patients with Hurler-Scheie or Scheie syndrome age 18 or greater who have not had ERT for at least 7 days prior to starting treatment. Approximately 3 cohorts will be enrolled sequentially, with safety data from the previous cohort being reviewed prior to escalation to the next higher dose cohort. Patients will be assigned to cohorts on the basis of their order of entry into the study.

The first cohort will be administered a single intravenous infusion of 0.3 mg/kg AGT-181 diluted in D5 normal saline over 4 hours. All patients will be observed for safety for 28 days after dosing. For dose escalation, the decision to proceed to a higher dose of AGT-181 will be made by the Sponsor and the investigator(s) after review of the available safety and tolerability data on or after 7 days post dose from patients who received the previous dose.

Dose escalation to a higher dose cohort can occur providing there are no dose limiting toxicities (DLT), defined as Grade 3 (severe or medically significant but not immediately life threatening) or higher adverse event according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

Stage 2:

Assuming safety and tolerability in Stage 1, a second stage will be initiated using a multi-dose, safety, tolerability and proof of concept effect design in children (age 2 or older) with Hurler or Hurler-Scheie with CNS involvement who are either ERT naïve or will have not received ERT for at least 7 days prior to first dose of AGT-181.

This second stage of the study will be conducted in dose groups of up
Sponsor: ArmaGen, Inc

Current Primary Outcome:

  • Stage 1: number of patients with adverse events as a measure of safety and tolerability of a single dose [ Time Frame: 4 weeks ]
  • Stage 2: number of patients with adverse events as a measure of safety and tolerability of repeat weekly doses [ Time Frame: 26 weeks ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • PK parameters (maximal concentration, half-life, AUC, distribution and clearance) of AGT-181 [ Time Frame: 26 weeks ]
  • change in total urinary glycosaminoglycans (GAGs) [ Time Frame: 26 weeks ]
  • change in functional capacity (6-minute walk test) or lung function (forced vital capacity) [ Time Frame: 26 weeks ]
  • change in shoulder range of motion (ROM) [ Time Frame: 26 weeks ]
  • change in liver and/or spleen volume (measured by MRI) [ Time Frame: 26 weeks ]


Original Secondary Outcome:

Information By: ArmaGen, Inc

Dates:
Date Received: February 9, 2017
Date Started: October 2015
Date Completion: October 2017
Last Updated: February 27, 2017
Last Verified: February 2017